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So far the focus has been on treating patients who have been infected. But perhaps the most exciting potential use of antivirals is as a prophylaxis, a preventive treatment given to people before they test positive.
Paxlovid and molnupiravir work in slightly different ways, but both aim to stop the virus replicating once it has infected human cells. If given after someone has contracted the virus, this stops the viral load rising to a level at which they become severely ill. They might suffer mild symptoms, but it will hopefully stop them needing hospital care.
If given before the virus reaches the body, however, antivirals can stop it taking hold. This preventive approach is being trialled simultaneously by Pfizer, MSD and the NIHR, with uninfected adult family members given the drug as soon as their relatives test positive.
No results have yet been produced but there is strong precedent for the use of drugs in this way. HIV treatment has been revolutionised in the past decade by the use of antivirals as pre-exposure prophylaxis (PrEP), with those who take these drugs receiving 99 per cent protection from sexual transmission. Some at-risk people, including some gay and bisexual men, take the drug every day to prevent risk of contracting the virus: the “pre- exposure” approach. Others take a “post-exposure” course if they believe they have had unprotected sex with someone who has HIV.
Covid, of course, is not HIV. But a similar approach could be taken for future coronavirus outbreaks. One route — the “post-exposure” route — would be to give the treatment to close contacts of those who test positive, as is being trialled for family members. Another approach — the “pre-exposure” route — would be to give the treatment to those in high-risk settings.
In the future, if an outbreak were to hit a care home, for example, all residents and staff could be given the drug. If a bigger wave arrived, all elderly and vulnerable people in the country could receive a prescription.
Daria Hazuda, vice-president of infectious disease and vaccine discovery at MSD, said: “Using these kinds of drugs as prophylaxis in high-risk individuals and high-risk settings will be very impactful at saving lives.” The scientist, who worked on HIV in the late 1980s and early 1990s, added: “For HIV we still don’t know how to make a good vaccine despite decades of trying.” Antivirals have filled the gap, providing almost 100 per cent protection as a preventive measure.
Antivirals are also attractive for another reason. If a catastrophic variant arrived that bypassed our vaccines, scientists are confident antivirals would remain effective. Annaliesa Anderson, chief scientist at Pfizer’s antivirals unit, said the way the drugs work mean they are unlikely to be affected by any future variants, pointing to data published last week showing paxlovid is completely unaffected by Omicron.
“Variants of concern are driven by changes in the spike protein, which is the target of the vaccine,” Anderson said. But antivirals do not interact with the spike protein. Paxlovid instead attacks the main protease, an enzyme the virus uses to replicate.
“The main protease is very well conserved within Sars-Cov-2,” Anderson said. Not only does this remain unchanged between Covid variants, but also between other coronaviruses, such as Sars-1 and Mers. “It is very encouraging: if we see another emerging coronavirus it gives us an opportunity for a very rapid treatment,” she said.
Molnupiravir works in a different way, inserting itself into viral RNA — the genetic material at the heart of the virus — and causing errors that stop it replicating. But this mechanism is also unaffected by variants. Hazuda said: “It will be very challenging for the virus to evolve resistance.” Molnupiravir, like paxlovid, seems to work across different coronaviruses, but studies suggest it will also work against influenza — including the avian flu strains that scientists view as the biggest threat of a future pandemic.
The Covid wave is receding. Restrictions are being eased. But the virus itself has not gone away. There will be future outbreaks and future waves. Combined with vaccines, however, antivirals promise to help ensure that Covid never again causes the kind of death and disruption we have seen during the past two years. And if another virus rears its head, these drugs provide the starting point for a new pandemic defence.
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